Acidic processes to prepare antimicrobial contact lenses

ABSTRACT

This invention relates to antimicrobial lenses containing metals and methods for their production.

RELATED APPLICATION

This application is a non-provisional filing of a provisionalapplication, U.S. Ser. No. 60/863,583, filed on Oct. 31, 2006.

FIELD OF THE INVENTION

This invention relates to methods of preparing antimicrobial lenses

BACKGROUND OF THE INVENTION

Contact lenses have been used commercially to improve vision since the1950s. The first contact lenses were made of hard materials. They wereused by a patient during waking hours and removed for cleaning. Currentdevelopments in the field gave rise to soft contact lenses, which may beworn continuously, for several days or more without removal forcleaning. Although many patients favor these lenses due to theirincreased comfort, these lenses can cause some adverse reactions to theuser. The extended use of the lenses can encourage the buildup ofbacteria or other microbes, particularly, Pseudomonas aeruginosa, on thesurfaces of soft contact lenses. The build-up of bacteria and othermicrobes can cause adverse side effects such as contact lens acute redeye and the like. Although the problem of bacteria and other microbes ismost often associated with the extended use of soft contact lenses, thebuild-up of bacteria and other microbes occurs for users of hard contactlens wearers as well.

Others have taught that the addition of antibacterial agents such asmetal salts to contact lenses can inhibit the growth of bacteria orother microbes. See, US 2004/0150788, which is hereby incorporated byreference in its entirety. In order produce manufacturing quantities ofcontact lenses containing antibacterial agents, processes to preparethese lenses must give consistent results. When some of the processesdisclosed in US 2004-0150788 are used with different contact lensformulations, the contact lenses that are produced have variable amountsof antibacterial agents contained therein. Since the amount ofantibacterial agent in every lens must be consistent from lot to lot, itis desirable to find process to prepare contact lenses containingantibacterial agents that produce a consistent product. This need is metby the following invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 Silver content vs Sodium Iodide concentration in a neutralprocess.

FIG. 2. Silver content vs Sodium Iodide in an acidified process.

DETAILED DESCRIPTION OF THE INVENTION

This invention includes a method of preparing an antimicrobial lenscomprising, consisting essentially of, or consisting of a metal salt,wherein said method comprising the steps of

-   -   (a) treating a cured lens, a solution comprising, consisting        essentially of, or consisting of a salt precursor and an        effective amount of an acidic substance, wherein the pH of said        solution is less than about 7.0; and    -   (b) treating the lens of step (a) with a solution comprising,        consisting essentially of, or consisting of a metal agent and an        effective amount of an acidic substance, wherein the pH of said        solution is less than about 7.0.        As used herein, the term, “antimicrobial lens” means a lens that        exhibits one or more of the following properties, the inhibition        of the adhesion of bacteria or other microbes to the lenses, the        inhibition of the growth of bacteria or other microbes on        lenses, and the killing of bacteria or other microbes on the        surface of lenses or in an area surrounding the lenses. For        purposes of this invention, adhesion of bacteria or other        microbes to lenses, the growth of bacteria or other microbes on        lenses and the presence of bacteria or other microbes on the        surface of lenses are collectively referred to as “microbial        colonization.” Preferably, the lenses of the invention exhibit a        reduction of viable bacteria or other microbe of at least about        0.25 log, more preferably at least about 0.5 log, most        preferably at least about 1.0 log L>90% inhibition). Such        bacteria or other microbes include but are not limited to those        organisms found in the eye, particularly Pseudomonas aeruginosa,        Acanthamoeba species, Staphylococcus. aureus, Escherichia. coli,        Staphylococcus epidermidis, and Serratia marcesens.

As used herein, the term “acidic substance” refers to a composition maybe added to a solution to reduce the pH of said solution to a pH of lessthan 7. Examples of acidic substances include but are not limited toacetic acid, sulfuric acid, and hydrochloric acid. The preferred acidicsubstance is acetic acid. The term “effective amount” refers to theconcentration of the acidic substance required to reduce the pH of thesolution to less than 7. It is preferable that the effective amountreduce the pH of the solution to less, than about 5, more preferably toless than about 4, most preferably less than about 3.6. The preferredacidic substance, acetic acid, is present in a concentration of about0.01% to about 10% (weight percent, based on the total weight of thesolution), more preferably about 0.5%, most preferably about 0.05%. Theacidic substance in step (a) and step (b) may be the same or different.It is preferred that the acidic substance of steps (a) and (b) are thesame.

As use herein, the term “metal salt” means any molecule having thegeneral formula [M]_(a) [X]_(b) wherein X contains any negativelycharged ion, a is >1, b is >1 and M is any positively charged metalselected from, but not limited to, the following Al⁺³, Co⁺², Co⁺³, Ca⁺²,Mg⁺², Ni⁺², Ti⁺², Ti⁺³, Ti⁺⁴, V⁺², V⁺³, V⁺⁵, Sr⁺², Fe⁺², Fe⁺³, Ag⁺¹,Ag⁺², Au⁺², Au⁺³, Au⁺¹, Pd⁺², Pd⁺⁴, Pt⁺², Pt⁺⁴ Cu⁺¹ Cu⁺², Mn⁺², Mn⁺³,Mn⁺⁴, Zn⁺², and the like. Examples of X include but are not limited toCO₃ ⁻², NO₃ ⁻¹, PO₄ ⁻³, Cl⁻¹, I⁻¹, Br⁻¹, S⁻², O⁻² and the like. FurtherX includes negatively charged ions containing CO₃ ⁻² NO₃ ⁻¹, PO₄ ⁻³,Cl⁻¹, I⁻¹, Br⁻¹, S⁻², O⁻², and the like, such as C₁₋₅alkylCO₂ ⁻¹. Asused herein the term metal salts does not include zeolites, disclosed inWO03/011351. This patent application is hereby incorporated by referencein its entirety. The preferred a is 1, 2, or 3. The preferred b is 1, 2,or 3. The preferred metals ions are Mg⁺², Zn⁺², Cu⁺¹, Cu⁺², Au⁺², Au⁺³,Au⁺¹, Pd⁺², Pd⁺⁴, Pt⁺², Pt⁺⁴, Ag⁺², and Ag⁺¹. The particularly preferredmetal ion is Ag⁺¹. Examples of suitable metal salts include but are notlimited to manganese sulfide, zinc oxide, zinc sulfide, copper sulfide,and copper phosphate. Examples of silver salts include but are notlimited to silver nitrate, silver sulfate, silver iodate, silvercarbonate, silver phosphate, silver sulfide, silver chloride, silverbromide, silver iodide, and silver oxide. The preferred silver salts aresilver iodide, silver chloride, and silver bromide.

The amount of metal in the lenses is measured based upon the totalweight of the lenses. When the metal is silver, the preferred amount ofsilver is about 0.00001 weight percent (0.1 ppm) to about 10.0 weightpercent, preferably about 0.0001 weight percent (1 ppm) to about 1.0weight percent, most preferably about 0.001 weight percent (10 ppm) toabout 0.1 weight percent, based on the dry weight of the lens. Withrespect to adding metal salts, the molecular weight of the metal saltsdetermines the conversion of weight percent of metal ion to metal salt.The preferred amount of silver salt is about 0.00003 weight percent (0.3ppm) to about 30.0 weight percent, preferably about 0.0003 weightpercent (3 ppm) to about 3.0 weight percent, most preferably about 0.003weight percent (30 ppm) to about 0.3 weight percent, based on the dryweight of the lens.

The term “salt precursor” refers to any compound or composition(including aqueous solutions) that contains a cation that may besubstituted with metal ions. The concentration of salt precursor in itssolution is between about 0.00001 to about 10.0 weight percent,(0.1-100,000 ppm) more preferably about 0.0001 to about 1.0 weightpercent, (1-10,000 ppm) most preferably about 0.001 to about 0.1 weightpercent (10-1000 ppm) based upon the total weight of the solution.Examples of salt precursors include but are not limited to inorganicmolecules such as sodium chloride, sodium iodide, sodium bromide, sodiumsulfide, lithium chloride, lithium iodide, lithium bromide, lithiumsulfide, potassium bromide, potassium chloride, potassium sulfide,potassium iodide, rubidium iodide, rubidium bromide, rubidium chloride,rubidium sulfide, caesium iodide, caesium bromide, caesium chloride,caesium sulfide, francium iodide, francium bromide, francium chloride,francium sulfide, sodium tetrachloro argentite, and the like. Examplesof organic molecules include but are not limited to tetra-alkyl ammoniumlactate, tetra-alkyl ammonium sulfate, quaternary ammonium halides, suchas tetra-alkyl ammonium chloride, bromide or iodide. The preferred saltprecursor is selected from the group consisting of sodium chloride,sodium iodide, sodium bromide, lithium chloride, lithium sulfide, sodiumsulfide, potassium sulfide, potassium iodide, and sodium tetrachloroargentite and the particularly preferred salt precursor is sodiumiodide.

The term “metal agent” refers to any composition (including aqueoussolutions) containing metal ions. Examples of such compositions includebut are not limited to aqueous or organic solutions of silver nitrate,silver triflate, or silver acetate, silver tetrafluoroborate, silversulfate, zinc acetate, zinc sulfate, copper acetate, and copper sulfate,where the concentration of metal agent in solution is about 1 μg/mL orgreater. The preferred metal agent is aqueous silver nitrate, where theconcentration of silver nitrate is the solution is about greater than orequal to 0.0001 to about 2 weight percent, more preferably about greaterthan 0.001 to about 0.01 weight percent based on the total weight of thesolution.

The term “solution” refers to an aqueous substance such as deionizedwater, saline solutions, borate or buffered saline solution, or organicsubstance such as C1-C24 alcohols, cyclic amides, acyclic amides, ethersand acids.

The term “treating” refers to any method of contacting solutions of themetal agent and the acidic substance or, the salt precursor and theacidic substance, with the lens, where the preferred method is immersingthe lens in a solution of containing either the metal agent and theacidic substance or the salt precursor and the acidic substance.Treating can include heating the lens in these solutions, but itpreferred that treating is carried out at ambient temperatures. The timeof treating is preferably about 1 minute to 24 hours, most preferablyabout 3 minute to about 30 minutes

As used herein, the term “lens” refers to an ophthalmic device thatresides in or on the eye. These devices can provide optical correction,wound care, drug delivery, diagnostic functionality, cosmeticenhancement or effect or a combination of these properties. The termlens includes but is not limited to soft contact lenses, hard contactlenses, intraocular lenses, overlay lenses, ocular inserts, and opticalinserts. Soft contact lenses are made from silicone elastomers orhydrogels, which include but are not limited to silicone hydrogels, andfluorohydrogels.

For example the term lens includes but is not limited to those made fromthe soft contact lens formulations described in U.S. Pat. No. 5,710,302,WO 9421698, EP 406161, JP 2000016905, U.S. Pat. No. 5,998,498, U.S.patent application Ser. No. 09/532,943, U.S. Pat. No. 6,087,415, U.S.Pat. No. 5,760,100, U.S. Pat. No. 5,776,999, U.S. Pat. No. 5,789,461,U.S. Pat. No. 5,849,811, and U.S. Pat. No. 5,965,631. Examples of softcontact lenses formulations include but are not limited to theformulations of etafilcon A, balafilcon A, bufilcon A, deltafilcon A,droxifilcon A, phemfilcon A, ocufilicon A, perfilcon A, ocufilcon B,ocufilcon C, ocufilcon D, ocufilcon E, metafilcon A, B, vifilcon Afocofilcon A, tetrafilcon B, and silicone hydrogels, as prepared in U.S.Pat. No. 5,998,498, U.S. Ser. No. 09/532,943, a continuation-in-part ofU.S. patent application Ser. No. 09/532,943, filed on Aug. 30, 2000,WO03/22321, U.S. Pat. No. 6,087,415, U.S. Pat. No. 5,760,100, U.S. Pat.No. 5,776,999, U.S. Pat. No. 5,789,461, U.S. Pat. No. 5,849,811, andU.S. Pat. No. 5,965,631. These patents as well as all other patentdisclosed in this paragraph are hereby incorporated by reference intheir entirety.

Lenses of the invention may be made from silicone hydrogel components. Asilicone-containing component is one that contains at least one[—Si—O—Si] group, in a monomer, macromer or prepolymer. Preferably, theSi and attached O are present in the silicone-containing component in anamount greater than 20 weight percent, and more preferably greater than30 weight percent of the total molecular weight of thesilicone-containing component. Useful silicone-containing componentspreferably comprise polymerizable functional groups such as acrylate,methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinylamide,and styryl functional groups. Examples of silicone components which maybe included in the silicone hydrogel formulations include, but are notlimited to silicone macromers, prepolymers and monomers. Examples ofsilicone macromers include, without limitation, polydimethylsiloxanemethacrylated with pendant hydrophilic groups as described in U.S. Pat.Nos. 4,259,467; 4,260,725 and 4,261,875; polydimethylsiloxane macromerswith polymerizable functional group(s) described in U.S. Pat. Nos.4,136,250; 4,153,641; 4,189,546; 4,182,822; 4,343,927; 4,254,248;4,355,147; 4,276,402; 4,327,203; 4,341,889; 4,486,577; 4,605,712;4,543,398; 4,661,575; 4,703,097; 4,837,289; 4,954,586; 4,954,587;5,346,946; 5,358,995; 5,387,632; 5,451,617; 5,486,579; 5,962,548;5,981,615; 5,981,675; and 6,039,913; polysiloxane macromersincorporating hydrophilic monomers such as those described in U.S. Pat.Nos. 5,010,141; 5,057,578; 5,314,960; 5,371,147 and 5,336,797; macromerscomprising polydimethylsiloxane blocks and polyether blocks such asthose described in U.S. Pat. Nos. 4,871,785 and 5,034,461, combinationsthereof and the like. All of the patents cited herein are herebyincorporated in their entireties by reference.

The silicone and/or fluorine containing macromers described in U.S. Pat.Nos. 5,760,100; 5,776,999; 5,789,461; 5,807,944; 5,965,631 and 5,958,440may also be used. Suitable silicone monomers includetris(trimethylsiloxy)silylpropyl methacrylate, hydroxyl functionalsilicone containing monomers, such as3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilaneand those disclosed in WO03/22321, and mPDMS containing or the siloxanemonomers described in U.S. Pat. Nos. 4,120,570, 4,139,692, 4,463,149,4,450,264, 4,525,563; 5,998,498; 3,808,178; 4,139,513; 5,070,215;5,710,302; 5,714,557 and 5,908,906.

Additional suitable siloxane containing monomers include, amide analogsof TRIS described in U.S. Pat. No. 4,711,943, vinylcarbamate orcarbonate analogs described in U.S. Pat. No. 5,070,215, and monomerscontained in U.S. Pat. No. 6,020,445, monomethacryloxypropyl terminatedpolydimethylsiloxanes, polydimethylsiloxanes,3-methacryloxypropylbis(trimethylsiloxy)methylsilane,methacryloxypropylpentamethyl disiloxane and combinations thereof.

In addition to soft contact lens formulations, hard contact lenses maybe used. Examples of hard contact lens formulations are made frompolymers that include but are not limited to polymers ofpoly(methyl)methacrylate, silicon acrylates, silicone acrylates,fluoroacrylates, fluoroethers, polyacetylenes, and polyimides, where thepreparation of representative examples may be found in JP 200010055, JP6123860 and U.S. Pat. No. 4,330,383. Intraocular lenses of the inventioncan be formed using known materials. For example, the lenses may be madefrom a rigid material including, without limitation, polymethylmethacrylate, polystyrene, polycarbonate, or the like, and combinationsthereof. Additionally, flexible materials may be used including, withoutlimitation, hydrogels, silicone materials, acrylic materials,fluorocarbon materials and the like, or combinations thereof. Typicalintraocular lenses are described in WO 0026698, WO 0022460, WO 9929750,WO 9927978, WO 0022459, and JP 2000107277. U.S. Pat. Nos. 4,301,012;4,872,876; 4,863,464; 4,725,277; 4,731,079. All of the referencesmentioned in this application are hereby incorporated by reference intheir entirety.

Preferably, the lenses of the invention are optically clear, withoptical clarity comparable to lenses such as lenses made from etafilconA, genfilcon A, galyfilcon A, lenefilcon A, polymacon, acquafilcon A,balafilcon A, and lotrafilcon A. The most preferred lens formulationsare those used to prepare ionic lenses. Monomers that are useful in thepreparation of such lenses include methacrylic acid and the like.Examples of the most preferred lens formulations include those used toprepare etafilcon A, balafilcon A, bufilcon A, deltafilcon A,droxifilcon A, phemfilcon A, ocufilicon A, perfilcon A, ocufilcon B,ocufilcon C, ocufilcon D, ocufilcon E, metafilcon A, B, vifilcon Afocofilcon A, and tetrafilcon B

Many of the lens formulations cited above may allow a user to insert thelenses for a continuous period of time ranging from one day to thirtydays. It is known that the longer a lens is on the eye, the greater thechance that bacteria and other microbes will build up on the surface ofthose lenses. Therefore there is a need to develop lenses that releaseantimicrobial agents such as silver, over an extended period of time.

The term “cured” refers to any of a number of methods used to react amixture of lens components (ie, momoner, prepolymers, macromers and thelike) to form lenses. Lenses can be cured by light or heat. Thepreferred method of curing is with radiation, preferably UV or visiblelight, and most preferably with visible light. The lens formulations ofthe present invention can be formed by any of the methods know to thoseskilled in the art, such as shaking or stirring, and used to formpolymeric articles or devices by known methods.

For example, the antimicrobial lenses of the invention may be preparedby mixing reactive components and any diluent(s) with a polymerizationinitiator and curing by appropriate conditions to form a product thatcan be subsequently formed into the appropriate shape by lathing,cutting and the like. Alternatively, the reaction mixture may be placedin a mold and subsequently cured into the appropriate article.

Various processes are known for processing the lens formulation in theproduction of contact lenses, including spincasting and static casting.Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429 and3,660,545, and static casting methods are disclosed in U.S. Pat. Nos.4,113,224 and 4,197,266. The preferred method for producingantimicrobial lenses of this invention is by molding. In the case ofhydrogel lenses, for this method, the lens formulation is placed in amold having the approximate shape of the final desired lens, and thelens formulation is subjected to conditions whereby the componentspolymerize, to produce a hardened disc that is subjected to a number ofdifferent processing steps including treating the polymerized lens withliquids (such as water, inorganic salts, or organic solutions) to swell,or otherwise equilibrate this lens prior to enclosing the lens in itsfinal packaging. This method is further described in U.S. Pat. Nos.4,495,313; 4,680,336; 4,889,664; and 5,039,459, incorporated herein byreference. Polymerized lenses that have not been swelled or otherwiseequilibrated are considered cured lenses for purposes of this invention.

Further, the invention includes a method of preparing an antimicrobiallens comprising, consisting essentially of, or consisting of a metalsalt, wherein the method comprises, consists essentially of, or consistsof the steps of

-   -   (a) treating a cured lens, a solution comprising, consisting        essentially of, or consisting of a metal agent and an effective        amount of an acidic substance, wherein the pH of said solution        is less than about 7.0; and    -   (b) treating the lens of step (a) with a solution comprising,        consisting essentially of, or consisting of a salt precursor and        an effective amount of an acidic substance, wherein the pH of        said solution is less than about 7.0.        The terms antimicrobial lens, metal salt, salt precursor, metal        agent, effective amount and treating all have their        aforementioned meanings and preferred ranges.

Still further the invention includes an antimicrobial lens comprising,consisting essentially of, or consisting of a metal salt, prepared by amethod comprising the steps of

-   -   (a) treating a cured lens, a solution comprising, consisting        essentially of, or consisting of a salt precursor and an        effective amount of an acidic substance, wherein the pH of said        solution is less than about 7.0; and    -   (b) treating the lens of step (a) with a solution comprising,        consisting essentially of, or consisting of a metal agent and an        effective amount of an acidic substance, wherein the pH of said        solution is less than about 7.0.        The terms antimicrobial lens, metal salt, salt precursor, metal        agent, effective amount and treating all have their        aforementioned meanings and preferred ranges.

Yet still further, the invention includes an antimicrobial lenscomprising, consisting essentially of, or consisting of a metal salt,prepared by a method comprising the steps of

-   -   (a) treating a cured lens, a solution comprising, consisting        essentially of, or consisting of a metal agent and an effective        amount of an acidic substance, wherein the pH of said solution        is less than about 7.0; and    -   (b) treating the lens of step (a) with a solution comprising,        consisting essentially of, or consisting of a salt precursor and        an effective amount of an acidic substance, wherein the pH of        said solution is less than about 7.0.        The terms antimicrobial lens, metal salt, salt precursor, metal        agent, effective amount and treating all have their        aforementioned meanings and preferred ranges.

In order to illustrate the invention the following examples areincluded. These examples do not limit the invention. They are meant onlyto suggest a method of practicing the invention. Those knowledgeable incontact lenses as well as other specialties may find other methods ofpracticing the invention. However, those methods are deemed to be withinthe scope of this invention.

EXAMPLES

The following abbreviations were used in the examples

Blue HEMA=the reaction product of reactive blue number 4 and HEMA, asdescribed in Example 4 or U.S. Pat. No. 5,944,853

CGI 819=bis(2,4,6-trimethylbenzoyl)phenylphosphineoxide

DI water=deionized water

DMA=N,N-dimethylacrylamide

HEMA=hydroxyethyl methacrylate

MAA=methacrylic acid;

mPDMS=mono-methacryloxypropyl terminated polydimethylsiloxane (MW800-1000)

acPDMS=bis-3-acryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane

Norbloc=2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole

ppm=parts per million micrograms of sample per gram of dry lens

PVP=polyvinylpyrrolidinone (360,000 or 2,500)

Simma 2=3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane

TAA=t-amyl alcohol

Sodium Sulfate Packing Solution (SSPS)

SSPS contains the following in deionized H₂O:

1.40 weight % sodium sulfate

0.185 weight % sodium borate [1330-43-4], Mallinckrodt

0.926 weight % boric acid [10043-35-3], Mallinckrodt

0.005 weight % methylcellulose

Preparation Lens Type A

A hydrogel blend was made from the following monomer mix (all amountswere calculated as weight percent: 30.00% SIMM 2, 28.0% mPDMS, 5.0%acPDMS, 19.0% DMA, 7.15% HEMA, 1.60% MM, 7.00% PVP 360,000, 2.0%Norbloc, 1.0% CGI 819 and 0.02% Blue HEMA, 60 weight percent of thepreceding component mixture was further diluted with diluent, 40 weightpercent of 72.5:27.5 TAA: PVP 2,500, to form the final monomer mix. Theblend placed in a two part contact lens mold and was cured using thefollowing sequential conditions a) room temperature for 30 seconds usinga visible light that emits 1 mW/sq cm, b)75° C. 120 seconds, c) 75° C.120 seconds 1.8 mW/sq/cm, and d) 75° C. 240 seconds 6.0 mW/sq cm. Thecured lenses are removed from the molds and hydrated with Di.

Example 1 Preparation of Antimicrobial Lenses from Cured Lenses withoutan Acidic Substance

Cured and hydrated lenses of Type A are placed in a jar with sodiumiodide solution in deionized water (500-700 ppm), containing 50 ppm ofmethylcellulose (˜3 mL solution per lens,) and rolled on a jar rollerovernight. The lenses were transferred from the jar to a blister packwhere the excess sodium iodide solution was removed. A solution (800 μL,150 ppm) of silver nitrate in deionized water, containing theappropriate dispersion agent, was added to the blister for two to fiveminutes. The silver nitrate solution was removed, and the lenses wereplaced in a jar containing deionized water and rolled on a jar rollerfor approximately thirty minutes. The deionized water was replaced withborate buffered sodium sulfate solution containing 50 ppmmethylcellulose water (SSPS), and allowed to roll on the jar roller foran additional 30 minutes. The solution was then replaced with freshSSPS.

The lenses were then transferred to new blisters and dosed with 950 μLof SSPS. The blisters were sealed and autoclaved at 125° C. for 18minutes and analyzed for silver content using the method describedbelow. The results are presented in FIG. 1. This data shows thatincreasing the concentration of sodium iodide, unexpectedly reduces theamount of silver iodide deposited into the lens.

Silver content of the lenses after lens autoclaving was determined byInstrumental Neutron Activation Analysis “INAA”. INAA is a qualitativeand quantitative elemental analysis method based on the artificialinduction of specific radionuclides by irradiation with neutrons in anuclear reactor. Irradiation of the sample is followed by thequantitative measurement of the characteristic gamma rays emitted by thedecaying radionuclides. The gamma rays detected at a particular energyare indicative of a particular radionuclide's presence, allowing for ahigh degree of specificity. Becker, D. A.; Greenberg, R. R.; Stone, S.F. J. Radioanal. Nucl. Chem. 1992, 160(1), 41-53; Becker, D. A.;Anderson, D. L.; Lindstrom, R. M.; Greenberg, R. R.; Garrity, K. M.;Mackey, E. A. J. Radioanal. Nucl. Chem. 1994, 179(1), 149-54. The INAAprocedure used to quantify silver content in contact lens material usesthe following two nuclear reactions:

-   -   1. In the activation reaction, ¹¹⁰Ag is produced from stable        ¹⁰⁹Ag (isotopic abundance=48.16%) after capture of a radioactive        neutron produced in a nuclear reactor.    -   2. In the decay reaction, ¹¹⁰Ag (τ^(1/2)=24.6 seconds) decays        primarily by negatron emission proportional to initial        concentration with an energy characteristic to this        radio-nuclide (657.8 keV).        The gamma-ray emission specific to the decay of ¹¹⁰Ag from        irradiated. standards and samples are measured by gamma-ray        spectroscopy, a well-established pulse-height analysis        technique, yielding a measure of the concentration of the        analyte.

Example 2 Preparation of Antimicrobial Lenses from Cured Lenses with anAcidic Substance

The procedure of Example 1 was repeated with one exception, 0.05% weightpercent of Acetic Acid in deionized water was added to the sodium iodidesolution and the silver nitrate solution. The lenses were analyzed forsilver content and the data is presented in FIG. 2. This data shows thatthe acidified process gives the expected increase in the amount ofsilver iodide deposited in the lens as the amount of sodium nitrate isincreased.

1. A method of preparing an antimicrobial lens comprising a metal salt,wherein said method comprising the steps of (a) treating a cured lens, asolution comprising, consisting essentially of, or consisting of a saltprecursor and an effective amount of an acidic substance, wherein the pHof said solution is less than about 7.0; and (b) treating the lens ofstep (a) with a solution comprising, consisting essentially of, orconsisting of a metal agent and an effective amount of an acidicsubstance, wherein the pH of said solution is less than about 7.0. 2.The method of claim 1 wherein the acidic substance is selected from thegroup consisting of acetic acid, hydrochloric acid, and sulfuric acid.3. The method of claim 1 wherein the acidic substance is acetic acid. 4.The method of claim 1 wherein the effective amount of the acidicsubstance is about 0.01% to about 10%.
 5. The method of claim 1 whereinthe effective amount of the acidic substance is about 0.5%.
 6. Themethod of claim 1 wherein the effective amount of the acidic substanceis about 0.05%.
 7. The method of claim 1 wherein the ph of the solutionof steps (a) and (b) is about 2 to about
 5. 8. The method of claim 1wherein the ph of the solution of steps (a) and (b) is about 2 to about4.
 9. The method of claim 1 wherein the pH of the solution of steps (a)and (b) is about 3 to about
 4. 10. The method of claim 1 wherein thesalt precursor is selected from the group consisting of tetra-alkylammonium lactate, tetra-alkyl ammonium sulfate, tetra-alkyl ammoniumchloride, tetra-alkyl ammonium, bromide, tetra-alkyl ammonium iodide,sodium chloride, sodium iodide, sodium bromide, lithium chloride,lithium sulfide, sodium sulfide, potassium sulfide, and sodiumtetrachloro argentate.
 11. The method of claim 1 wherein the saltprecursor is selected from the group consisting of sodium chloride,sodium iodide, sodium bromide, lithium chloride, lithium sulfide, sodiumsulfide, potassium sulfide, and sodium tetrachloro argentite.
 12. Themethod of claim 1 wherein the salt precursor is sodium iodide.
 13. Themethod of claim 1 wherein the metal agent is selected from the groupconsisting of silver iodide, silver chloride, and silver bromide. 14.The method of claim 1 wherein the salt precursor is selected from thegroup consisting of silver nitrate, silver triflate, and silver acetate.15. The method of claim 1 wherein the salt precursor is silver acetate.16. A method of preparing an antimicrobial lens comprising a metal salt,wherein said method comprising the steps of (a) treating a cured lens, asolution comprising, consisting essentially of, or consisting of a metalagent and an effective amount of an acidic substance, wherein the pH ofsaid solution is less than about 7.0; and (b) treating the lens of step(a) with a solution comprising, consisting essentially of, or consistingof a salt precursor and an effective amount of an acidic substance,wherein the pH of said solution is less than about 7.0.
 17. Anantimicrobial lens comprising a metal salt, prepared by a methodcomprising the steps of (a) treating a cured lens, a solution comprisinga salt precursor and an effective amount of an acidic substance, whereinthe pH of said solution is less than about 7.0; and (b) treating thelens of step (a) with a solution comprising a metal agent and aneffective amount of an acidic substance, wherein the pH of said solutionis less than about 7.0.
 18. The antimicrobial lens of claim 17 whereinthe metal salt is silver iodide, the salt precursor is sodium nitrate,the metal agent is silver nitrate and the pH of the solutions of steps(a) and (b) is about 3-4.
 19. An antimicrobial lens comprising a metalsalt, prepared by a method comprising the steps of (a) treating a curedlens, a solution comprising a metal agent and an effective amount of anacidic substance, wherein the pH of said solution is less than about7.0; and (b) treating the lens of step (a) with a solution comprising,consisting essentially of, or consisting of a salt precursor and aneffective amount of an acidic substance, wherein the pH of said solutionis less than about 7.0.
 20. The antimicrobial lens of claim 19 whereinthe metal salt is silver iodide, the salt precursor is sodium nitrate,the metal agent is silver nitrate and the pH of the solutions of steps(a) and (b) is about 3-4.